Interactive effects of physical activity and APOE-ε4 on white matter tract diffusivity in healthy elders.
Interactive effects of physical activity and APOE-ε4 on white matter tract diffusivity in healthy elders.
复制标题
体育活动和APOE-ε4对健康长老中白质扩散率的互动效应。
DOI：
10.1016/j.neuroimage.2015.08.007
复制
发表时间：
2016-05-01
期刊：
影响因子：
5.7
通讯作者：
Rao SM
中科院分区：
文献类型：
--
作者：
Smith JC;Lancaster MA;Nielson KA;Woodard JL;Seidenberg M;Durgerian S;Sakaie K;Rao SM
老年人载脂蛋白E-ε 4（APOE-ε4）等位基因携带者在阿尔茨海默病（AD）临床症状的表达上差异很大，提示生活方式或其他因素可能对AD相关的神经退行性变提供保护。我们最近报道，与久坐的ε4等位基因携带者相比，身体活动的APOE-ε4等位基因携带者在18个月内表现出稳定的认知轨迹和对海马萎缩的保护。本研究的目的是研究AD遗传风险和身体活动（PA）之间的相互作用对白色（WM）束的完整性，使用扩散张量成像（DTI）MRI，在这个队列的健康老年人（年龄65至89岁）。根据是否存在APOE-ε4等位基因（高风险;低风险）和自我报告的休闲时间体力活动（PA）的频率和强度（高PA;低PA）对四组进行比较。正如预测的那样，在不具有APOE-ε4等位基因的健康老年人中，较高水平的PA与较高的各向异性分数（FA）和较低的径向扩散率相关。然而，PA的影响被逆转的老年人谁是在AD的遗传风险增加，导致PA和遗传风险之间的显着相互作用，在几个WM域。在高风险-低PA参与者中，与高风险-高PA参与者相比，在过去18个月内表现出情景记忆下降，径向扩散率较低，各向异性分数较高。在有助于学习和记忆过程的WM束中，径向扩散率（DR）与身体活动不活跃的APOE-ε4携带者的情景记忆表现呈负相关，而DR与身体活动活跃的APOE-ε4携带者和两个低风险组的情景记忆表现呈正相关。脱髓鞘引起的径向扩散率增加的常见模型不能直接解释这些结果。相反，我们假设PA可能保护APOE-ε4等位基因携带者在投射和联合WM纤维束内交叉纤维位置处的个体纤维群体的选择性神经变性。
Older adult apolipoprotein E epsilon 4 (APOE-ε4) allele carriers vary considerably in the expression of clinical symptoms of Alzheimer’s disease (AD), suggesting that lifestyle or other factors may offer protection from AD-related neurodegeneration. We recently reported that physically active APOE-ε4 allele carriers exhibit a stable cognitive trajectory and protection from hippocampal atrophy over 18 months compared to sedentary ε4 allele carriers. The aim of this study was to examine the interactions between genetic risk for AD and physical activity (PA) on white matter (WM) tract integrity, using diffusion tensor imaging (DTI) MRI, in this cohort of healthy older adults (ages of 65 to 89). Four groups were compared based on the presence or absence of an APOE-ε4 allele (High Risk; Low Risk) and self reported frequency and intensity of leisure time physical activity (PA) (High PA; Low PA). As predicted, greater levels of PA were associated with greater fractional anisotropy (FA) and lower radial diffusivity in healthy older adults who did not possess the APOE-ε4 allele. However, the effects of PA were reversed in older adults who were at increased genetic risk for AD, resulting in significant interactions between PA and genetic risk in several WM tracts. In the High Risk-Low PA participants, who had exhibited episodic memory decline over the previous 18-months, radial diffusivity was lower and fractional anisotropy was higher, compared to the High Risk-High PA participants. In WM tracts that subserve learning and memory processes, radial diffusivity (DR) was negatively correlated with episodic memory performance in physically inactive APOE-ε4 carriers, whereas DR was positively correlated with episodic memory performance in physically active APOE-ε4 carriers and the two Low Risk groups. The common model of demyelination-induced increase in radial diffusivity cannot directly explain these results. Rather, we hypothesize that PA may protect APOE-ε4 allele carriers from selective neurodegeneration of individual fiber populations at locations of crossing fibers within projection and association WM fiber tracts.